The Reprimo Gene Family: A Novel Gene Lineage in Gastric Cancer with Tumor Suppressive Properties

Int J Mol Sci. 2018 Jun 25;19(7):1862. doi: 10.3390/ijms19071862.

Abstract

The reprimo (RPRM) gene family is a group of single exon genes present exclusively within the vertebrate lineage. Two out of three members of this family are present in humans: RPRM and RPRM-Like (RPRML). RPRM induces cell cycle arrest at G2/M in response to p53 expression. Loss-of-expression of RPRM is related to increased cell proliferation and growth in gastric cancer. This evidence suggests that RPRM has tumor suppressive properties. However, the molecular mechanisms and signaling partners by which RPRM exerts its functions remain unknown. Moreover, scarce studies have attempted to characterize RPRML, and its functionality is unclear. Herein, we highlight the role of the RPRM gene family in gastric carcinogenesis, as well as its potential applications in clinical settings. In addition, we summarize the current knowledge on the phylogeny and expression patterns of this family of genes in embryonic zebrafish and adult humans. Strikingly, in both species, RPRM is expressed primarily in the digestive tract, blood vessels and central nervous system, supporting the use of zebrafish for further functional characterization of RPRM. Finally, drawing on embryonic and adult expression patterns, we address the potential relevance of RPRM and RPRML in cancer. Active investigation or analytical research in the coming years should contribute to novel translational applications of this poorly understood gene family as potential biomarkers and development of novel cancer therapies.

Keywords: biomarker; development; evolution; gastric cancer; reprimo; tumor suppressive gene properties.

Publication types

  • Review

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Cell Proliferation / genetics
  • DNA Methylation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Glycoproteins / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Promoter Regions, Genetic
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • Cell Cycle Proteins
  • Glycoproteins
  • Membrane Proteins
  • RPRM protein, human
  • RPRML protein, human